What is a mnemonic for cytochrome P450 enzyme inhibitors and inducers?

Mnemonics for Cytochrome P450 Enzyme Inhibitors and Inducers

The most clinically useful mnemonics for remembering CYP450 inhibitors and inducers are "SICKFACES.COM" for inhibitors and "PC BRAS" or "CRAP GPS" for inducers, which help clinicians quickly identify drugs that may cause significant drug-drug interactions through the CYP450 system.

CYP450 Inhibitors: "SICKFACES.COM"

The following mnemonic captures the major CYP450 inhibitors that increase drug levels by blocking metabolism 1:

• S - Sodium valproate, Sulfonamides (sulfamethoxazole/trimethoprim)
• I - Isoniazid, Itraconazole
• C - Cimetidine, Ciprofloxacin, Clarithromycin, Cyclosporine
• K - Ketoconazole
• F - Fluconazole, Fluoxetine, Fluvoxamine
• A - Amiodarone, Aprepitant
• C - Chloramphenicol
• E - Erythromycin
• S - Sertraline

Additional key inhibitors:

• C - Cranberry juice (grapefruit juice)
• O - Omeprazole
• M - Metronidazole, Macrolides

CYP450 Inducers: "PC BRAS" or "CRAP GPS"

These mnemonics identify drugs that decrease other drug levels by increasing metabolism 2, 1, 3:

"PC BRAS":

• P - Phenytoin, Phenobarbital
• C - Carbamazepine
• B - Barbiturates
• R - Rifampin, Rifabutin
• A - Alcohol (chronic use)
• S - St. John's Wort, Smoking

Alternative "CRAP GPS":

• C - Carbamazepine, Cyclophosphamide, Corticosteroids
• R - Rifampin
• A - Alcohol (chronic)
• P - Phenytoin, Phenobarbital, Pioglitazone
• G - Griseofulvin
• P - Phenobarbital
• S - St. John's Wort, Smoking

Clinical Application by CYP Isoform

CYP3A4 (Most Important - Metabolizes ~50% of Drugs)

Major Inhibitors 1, 4:

• Azole antifungals (ketoconazole, itraconazole, voriconazole)
• Macrolides (clarithromycin, erythromycin)
• Protease inhibitors (ritonavir)
• Calcium channel blockers (diltiazem, verapamil)
• Grapefruit juice
• Amiodarone

Major Inducers 2, 1, 5:

• Rifampin (most potent)
• Carbamazepine
• Phenytoin
• Phenobarbital
• St. John's Wort
• Efavirenz

CYP2D6

Major Inhibitors 1:

• Fluoxetine
• Paroxetine
• Quinidine
• Bupropion

CYP2C9

Major Inhibitors 2, 1:

• Amiodarone
• Fluconazole
• Metronidazole
• Sulfamethoxazole/trimethoprim
• Voriconazole

Inducers 4:

• Aprepitant
• Rifampin

CYP2C19

Major Inhibitors 2:

• Omeprazole
• Fluoxetine
• Fluvoxamine

Critical Clinical Considerations

When rifampin (strongest inducer) is used, expect dramatic reductions in substrate drug levels - the inductive effect of rifampin outweighs inhibitory effects of other drugs like isoniazid when used together 2. Rifampin induces CYP3A4, CYP2C9, and other pathways, requiring dose increases of concomitant medications that may need reversal within 2 weeks after rifampin discontinuation 2.

Erythromycin and clarithromycin are potent CYP3A4 inhibitors 6 that can cause dangerous interactions with drugs like cisapride, terfenadine, astemizole, and pimozide - these combinations are contraindicated due to risk of QT prolongation and torsades de pointes 6, 3.

Isoniazid inhibits CYP2C9, CYP2C19, and CYP2E1 (but not CYP3A4) 2, causing increased levels of phenytoin, carbamazepine, and benzodiazepines metabolized by oxidation (diazepam, triazolam) but not those metabolized by conjugation (oxazepam) 2.

Aprepitant has dual effects - it simultaneously acts as a CYP3A4 substrate, moderate inhibitor, AND moderate inducer, plus induces CYP2C9 4. This creates complex interactions requiring careful monitoring, particularly with warfarin (decreased INR), oral contraceptives (reduced efficacy), and chemotherapy agents metabolized by CYP3A4.

Protease inhibitors (boceprevir, telaprevir) are strong CYP3A4/5 inhibitors 3, contraindicated with simvastatin, lovastatin, oral midazolam, ergot derivatives, and Class I/III antiarrhythmics due to risk of severe toxicity including torsades de pointes 3.

Common Pitfalls to Avoid

• Don't assume all drugs in a class behave identically: Levofloxacin, gatifloxacin, and moxifloxacin do NOT inhibit theophylline metabolism like ciprofloxacin does 2
• Remember the time course: Enzyme induction takes days to weeks to develop and resolve; plan dose adjustments accordingly 2
• Consider multiple pathways: Many drugs are metabolized by multiple CYP isoforms plus P-glycoprotein and OATP transporters 1 - inhibition of one pathway may not fully predict clinical effects
• Genetic polymorphisms matter: CYP2D6 and CYP2C19 have significant genetic variability affecting baseline metabolizer status 7